Background: The Epstein–Barr virus (EBV) infects more than 90 percent of the human population. In pediatric patients, the innate immune response against EBV primary infection plays a key role. Monocytes and macrophages can have distinct functions depending on the microenvironment surrounding them. At least three monocyte subpopulations can be differentiated depending on membrane protein expression: classical (C, CD14++CD16−), intermediate (I, CD14++CD16+), and non-classical (NC, CD14+CD16++). They also modulate T and B lymphocyte activation/inhibition through the expression of costimulatory molecules such as CD80, CD86, and PD-L1. Yet, little is known about monocytes’ role in EBV infection.Methods: Peripheral blood and tonsil biopsies of EBV primary infected (PI) patients, healthy carriers (HCs), and patients undergoing reactivation (R) were studied.Results: Classical monocytes prevailed in all infectious statuses. Tonsillar CD163 positively correlated with CD163 expression in NC monocytes in HCs. PD-L1+ cells in the tonsil positively correlated with PD-L1 expression in NC monocytes. LMP-1 viral latent protein presented a positive correlation with PD-L1, CD163, and CD206 expression in the NC subpopulation.Conclusions: Our results evidence the predominant role of I and NC monocytes’ response against EBV infection. Furthermore, the viral oncoprotein LMP-1 could be involved in the expression of regulatory proteins in I and NC monocytes.
背景:爱泼斯坦-巴尔病毒(EBV)感染超过90%的人类群体。在儿科患者中,针对EBV原发性感染的先天免疫反应起着关键作用。单核细胞和巨噬细胞的功能可因其周围微环境而异。根据膜蛋白表达差异,至少可区分出三种单核细胞亚群:经典单核细胞(C型,CD14++CD16−)、中间单核细胞(I型,CD14++CD16+)和非经典单核细胞(NC型,CD14+CD16++)。这些细胞还通过表达CD80、CD86和PD-L1等共刺激分子调控T、B淋巴细胞的活化/抑制。然而,关于单核细胞在EBV感染中的作用仍知之甚少。 方法:本研究对EBV原发性感染(PI)患者、健康携带者(HCs)及再激活(R)患者的外周血和扁桃体活检样本进行分析。 结果:经典单核细胞在所有感染状态中均占主导地位。健康携带者扁桃体中CD163表达与NC单核细胞的CD163表达呈正相关。扁桃体中PD-L1阳性细胞与NC单核细胞的PD-L1表达呈正相关。病毒潜伏蛋白LMP-1在NC亚群中与PD-L1、CD163及CD206表达呈正相关。 结论:我们的研究结果证实了I型和NC型单核细胞在抗EBV感染反应中的主导作用。此外,病毒癌蛋白LMP-1可能参与调控I型和NC型单核细胞中调节性蛋白的表达。